Assessing receptivity to malaria using case surveillance and forest data in a near-elimination setting in northeast Thailand.

BACKGROUND: Thailand aimed to eliminate malaria by 2024, and as such is planning for future prevention of re-establishment in malaria free provinces. Understanding the receptivity of local areas to malaria allows the appropriate targeting of interventions. Current approaches to assessing receptivity involve collecting entomological data. Forest coverage is known to be associated with malaria risk, as an environment conducive to both vector breeding and high-risk human behaviours. METHODS: Geolocated, anonymized, individual-level surveillance data from 2011 to 2021 from the Thai Division of Vector-Borne Disease (DVBD) was used to calculate incidence and estimated Rc at village level. Forest cover was calculated using raster maps of tree crown cover density and year of forest loss from the publicly available Hansen dataset. Incidence and forest cover were compared graphically and using Spearman's rho. The current foci classification system was applied to data from the last 5 years (2017-2021) and forest cover for 2021 compared between the classifications. A simple risk score was developed to identify villages with high receptivity. RESULTS: There was a non-linear decrease in annual cases by 96.6% (1061 to 36) across the two provinces from 2011 to 2021. Indigenous Annual Parasite Index (API) and approximated Rc were higher in villages in highly forested subdistricts, and with higher forest cover within 5 km. Forest cover was also higher in malaria foci which consistently reported malaria cases each year than those which did not. An Rc > 1 was only reported in villages in subdistricts with > 25% forest cover. When applying a simple risk score using forest cover and recent case history, the classifications were comparable to those of the risk stratification system currently used by the DVBD. CONCLUSIONS: There was a positive association between forest coverage around a village and indigenous malaria cases. Most local transmission was observed in the heavily forested subdistricts on the international borders with Laos and Cambodia, which are where the most receptive villages are located. These areas are at greater risk of importation of malaria due to population mobility and forest-going activities. Combining forest cover and recent case surveillance data with measures of vulnerability may be useful for prediction of malaria recurrence risk.

Mapping malaria transmission foci in Northeast Thailand from 2011 to 2021: approaching elimination in a hypoendemic area.

BACKGROUND: Thailand is approaching local elimination of malaria in the eastern provinces. It has successfully reduced the number of cases over the past decade, but there are persistent transmission hot spots in and around forests. This study aimed to use data from the malaria surveillance system to describe the spatiotemporal trends of malaria in Northeast Thailand and fine-scale patterns in locally transmitted cases between 2011 and 2021. METHODS: Case data was stratified based on likely location of infection and parasite species. Annual Parasite Index per 1000 population (API) was calculated for different categories. Time series decomposition was performed to identify trends and seasonal patterns. Statistically significant clusters of high (hot spots) and low (cold spots) API were identified using the Getis-Ord Gi* statistic. The stability of those hot spots and the absolute change in the proportion of API density from baseline were compared by case type. RESULTS: The total number of confirmed cases experienced a non-linear decline by 96.6%, from 1061 in 2011 to 36 in 2021. There has been a decline in both Plasmodium vivax and Plasmodium falciparum case numbers, with only four confirmed P. falciparum cases over the last two years-a 98.89% drop from 180 in 2011. API was generally higher in Si Sa Ket province, which had peaks every 2-3 years. There was a large outbreak in Ubon Ratchathani in 2014-2016 which had a high proportion of P. falciparum reported. The proportion of cases classified increased over the study period, and the proportion of cases classed as indigenous to the village of residence increased from 0.2% to 33.3%. There were stable hot spots of indigenous and imported cases in the south of Si Sa Ket and southeast of Ubon Ratchathani. Plasmodium vivax hot spots were observed into recent years, while those of P. falciparum decreased to zero in Ubon in 2020 and emerged in the eastern part in 2021, the same year that P. falciparum hot spots in Si Sa Ket reached zero. CONCLUSIONS: There has been a large, non-linear decline in the number of malaria cases reported and an increasing proportion of cases are classed as indigenous to the patient's village of residence. Stable hot spots of ongoing transmission in the forested border areas were identified, with transmission likely persisting because of remote location and high-risk forest-going behaviours. Future efforts should include cross-border collaboration and continued targeting of high-risk behaviours to reduce the risk of imported cases seeding local transmission.

Projecting spatiotemporal dynamics of severe fever with thrombocytopenia syndrome in the mainland of China.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with increasing incidence and geographic extent. The extent to which global climate change affects the incidence of SFTS disease remains obscure. We use an integrated multi-model, multi-scenario framework to assess the impact of global climate change on SFTS disease in China. The spatial distribution of habitat suitability for the tick Haemaphysalis longicornis was predicted by applying a boosted regression tree model under four alternative climate change scenarios (RCP2.6, RCP4.5, RCP6.0, and RCP8.5) for the periods 2030-2039, 2050-2059, and 2080-2089. We incorporate the SFTS cases in the mainland of China from 2010 to 2019 with environmental variables and the projected distribution of H. longicornis into a generalized additive model to explore the current and future spatiotemporal dynamics of SFTS. Our results demonstrate an expanded geographic distribution of H. longicornis toward Northern and Northwestern China, showing a more pronounced change under the RCP8.5 scenario. In contrast, the environmental suitability of H. longicornis is predicted to be reduced in Central and Eastern China. The SFTS incidence in three time periods (2030-2039, 2050-2059, and 2080-2089) is predicted to be increased as compared to the 2010s in the context of various RCPs. A heterogeneous trend across provinces, however, was observed, when an increased incidence in Liaoning and Shandong provinces, while decreased incidence in Henan province is predicted. Notably, we predict possible outbreaks in Xinjiang and Yunnan in the future, where only sporadic cases have been reported previously. These findings highlight the need for tick control and population awareness of SFTS in endemic regions, and enhanced monitoring in potential risk areas.

Epidemiology of malaria in Rohingya refugee camps in Bangladesh within 2017-2020.

BACKGROUND: Malaria causes significant morbidity and mortality in tropical and sub-tropical regions, particularly in humanitarian emergencies including refugee camps in malaria endemic areas. An epidemiological investigation was conducted on malaria disease distribution and risk factors in the world's largest refugee settlement, the Rohingya refugee camps on the south-eastern border area of Bangladesh, within 2017-2020. METHODS: From February 2017 to March 2020, 30,460 febrile patients were tested for malaria using light microscopy and rapid diagnostic tests. Most were self-presenting symptomatic patients and a minority were from door-to-door malaria screening. Diagnostic tests were done by trained medical technologists upon the advice of the concerned physicians in the camps. Test positivity rate (%) and annual parasite incidence were calculated and compared using chi-squared (χ 2) test or odds ratios. RESULTS: The overall average annual test positivity rate (TPR) was 0.05%. TPR was highest in people who had travelled to the forest in the previous 2 months, at 13.60%. Cases were clustered among male adults aged 15-60 years. There were no cases among children under five years or pregnant women and no deaths from malaria. CONCLUSION: This study found very few malaria cases among Rohingya refugees with the majority of cases being imported from hilly forested areas, which were thus assumed to act as the reservoir for transmission.

Climate drives the spatiotemporal dynamics of scrub typhus in China.

Scrub typhus is a climate-sensitive and life-threatening vector-borne disease that poses a growing public health threat. Although the climate-epidemic associations of many vector-borne diseases have been studied for decades, the impacts of climate on scrub typhus remain poorly understood, especially in the context of global warming. Here we incorporate Chinese national surveillance data on scrub typhus from 2010 to 2019 into a climate-driven generalized additive mixed model to explain the spatiotemporal dynamics of this disease and predict how it may be affected by climate change under various representative concentration pathways (RCPs) for three future time periods (the 2030s, 2050s, and 2080s). Our results demonstrate that temperature, precipitation, and relative humidity play key roles in driving the seasonal epidemic of scrub typhus in mainland China with a 2-month lag. Our findings show that the change of projected spatiotemporal dynamics of scrub typhus will be heterogeneous and will depend on specific combinations of regional climate conditions in future climate scenarios. Our results contribute to a better understanding of spatiotemporal dynamics of scrub typhus, which can help public health authorities refine their prevention and control measures to reduce the risks resulting from climate change.

Improving knowledge, attitudes and practice to prevent COVID-19 transmission in healthcare workers and the public in Thailand.

BACKGROUND: Key infection prevention and control measures to limit transmission of COVID-19 include social distancing, hand hygiene, use of facemasks and personal protective equipment. However, these have limited or no impact if not applied correctly through lack of knowledge, inappropriate attitude or incorrect practice. In order to maximise the impact of infection prevention and control measures on COVID-19 spread, we undertook a study to assess and improve knowledge, attitudes and practice among 119 healthcare workers and 100 general public in Thailand. The study setting was two inpatient hospitals providing COVID-19 testing and treatment. Detailed information on knowledge, attitudes and practice among the general public and healthcare workers regarding COVID-19 transmission and its prevention were obtained from a combination of questionnaires and observations. RESULTS: Knowledge of the main transmission routes, commonest symptoms and recommended prevention methods was mostly very high (> 80%) in both groups. There was lower awareness of aerosols, food and drink and pets as sources of transmission; of the correct duration for handwashing; recommended distance for social/physical distancing; and about recommended types of face coverings. Information sources most used and most trusted were the workplace, work colleagues, health workers and television. The results were used to produce a set of targeted educational videos which addressed many of these gaps with subsequent improvements on retesting in a number of areas. This included improvements in handwashing practice with an increase in the number of areas correctly washed in 65.5% of the public, and 57.9% of healthcare workers. The videos were then further optimized with feedback from participants followed by another round of retesting. CONCLUSIONS: Detailed information on gaps in knowledge, attitudes and practice among the general public and healthcare workers regarding COVID-19 transmission and its prevention were obtained from a combination of questionnaires and observations. This was used to produce targeted educational videos which addressed these gaps with subsequent improvements on retesting. The resulting videos were then disseminated as a resource to aid in efforts to fight COVID-19 in Thailand and worldwide.

Estimating the programmatic cost of targeted mass drug administration for malaria in Myanmar.

BACKGROUND: Mass drug administration (MDA) has received growing interest to accelerate the elimination of multi-drug resistant malaria in the Greater Mekong Subregion. Targeted MDA, sometimes referred to as focal MDA, is the practice of delivering MDA to high incidence subpopulations only, rather than the entire population. The potential effectiveness of delivering targeted MDA was demonstrated in a recent intervention in Kayin State, Myanmar. Policymakers and funders need to know what resources are required if MDA, targeted or otherwise, is to be included in elimination packages beyond existing malaria interventions. This study aims to estimate the programmatic cost and the unit cost of targeted MDA in Kayin State, Myanmar. METHODS: We used financial data from a malaria elimination initiative, conducted in Kayin State, to estimate the programmatic costs of the targeted MDA component using a micro-costing approach. Three activities (community engagement, identification of villages for targeted MDA, and conducting mass treatment in target villages) were evaluated. We then estimated the programmatic costs of implementing targeted MDA to support P. falciparum malaria elimination in Kayin State. A costing tool was developed to aid future analyses. RESULTS: The cost of delivering targeted MDA within an integrated malaria elimination initiative in eastern Kayin State was approximately US$ 910,000. The cost per person reached, distributed among those in targeted and non-targeted villages, for the MDA component was US$ 2.5. CONCLUSION: This cost analysis can assist policymakers in determining the resources required to clear malaria parasite reservoirs. The analysis demonstrated the value of using financial data from research activities to predict programmatic implementation costs of targeting MDA to different numbers of target villages.

Mapping the stability of malaria hotspots in Bangladesh from 2013 to 2016.

BACKGROUND: Malaria claims hundreds of thousands of lives each year, most of them children. A "malaria-free world" is the World Health Organization's vision, but elimination from the southeast Asian Region is hampered by factors including anti-malarial resistance and systematic underreporting. Malaria is a significant public health problem in Bangladesh and while there have been recent gains in control, there is large spatial and temporal heterogeneity in the disease burden. This study aims to determine the pattern and stability of malaria hotspots in Bangladesh with the end goal of informing intervention planning for elimination. RESULTS: Malaria in Bangladesh exhibited highly seasonal, hypoendemic transmission in geographic hotspots, which remained conserved over time. The southeast areas of the Chittagong Hill Tracts were identified as malaria hotspots for all 4 years examined. Similarly, areas in Sunamganj and Netrakona districts in the Northeast were hotspots for 2013-2016. Highly stable hotspots from 1 year predicted the following year's hotspot locations in the southeast of Bangladesh. Hotspots did not appear to act as sources of spread with no evidence of consistent patterns of contiguous spread or recession of hotspots as high or low transmission seasons progressed. CONCLUSIONS: Areas were identified with temporal and spatial clustering of high malaria incidence in Bangladesh. Further studies are required to understand the vector, sociodemographic and disease dynamics within these hotspots. Given the low caseloads occurring in the low transmission seasons, and the conserved nature of malaria hotspots, directing resources towards these areas may be an efficient way to achieve malaria elimination in Bangladesh.

Magnetic resonance imaging of the brain in adults with severe falciparum malaria.

BACKGROUND: Magnetic resonance imaging (MRI) allows detailed study of structural and functional changes in the brain in patients with cerebral malaria. METHODS: In a prospective observational study in adult Bangladeshi patients with severe falciparum malaria, MRI findings in the brain were correlated with clinical and laboratory parameters, retinal photography and optic nerve sheath diameter (ONSD) ultrasound (a marker of intracranial pressure). RESULTS: Of 43 enrolled patients, 31 (72%) had coma and 12 (28%) died. MRI abnormalities were present in 79% overall with mostly mild changes in a wide range of anatomical sites. There were no differences in MRI findings between patients with cerebral and non-cerebral or fatal and non-fatal disease. Subtle diffuse cerebral swelling was common (n = 22/43), but mostly without vasogenic oedema or raised intracranial pressure (ONSD). Also seen were focal extracellular oedema (n = 11/43), cytotoxic oedema (n = 8/23) and mildly raised brain lactate on magnetic resonance spectroscopy (n = 5/14). Abnormalities were much less prominent than previously described in Malawian children. Retinal whitening was present in 36/43 (84%) patients and was more common and severe in patients with coma. CONCLUSION: Cerebral swelling is mild and not specific to coma or death in adult severe falciparum malaria. This differs markedly from African children. Retinal whitening, reflecting heterogeneous obstruction of the central nervous system microcirculation by sequestered parasites resulting in small patches of ischemia, is associated with coma and this process is likely important in the pathogenesis.

Retinal changes in visceral leishmaniasis by retinal photography.

BACKGROUND: In visceral leishmaniasis (VL), retinal changes have previously been noted but not described in detail and their clinical and pathological significance are unknown. A prospective observational study was undertaken in Mymensingh, Bangladesh aiming to describe in detail visible changes in the retina in unselected patients with VL. METHODS: Patients underwent assessment of visual function, indirect and direct ophthalmoscopy and portable retinal photography. The photographs were assessed by masked observers including assessment for vessel tortuosity using a semi-automated system. RESULTS: 30 patients with VL were enrolled, of whom 6 (20%) had abnormalities. These included 5 with focal retinal whitening, 2 with cotton wool spots, 2 with haemorrhages, as well as increased vessel tortuosity. Visual function was preserved. CONCLUSIONS: These changes suggest a previously unrecognized retinal vasculopathy. An inflammatory aetiology is plausible such as a subclinical retinal vasculitis, possibly with altered local microvascular autoregulation, and warrants further investigation.

Evaluation of an electronic clinical decision support algorithm to improve primary care management of acute febrile illness in rural Cambodia: protocol for a cluster-randomised trial.

INTRODUCTION: Acute febrile illness (AFI), traditionally attributed to malaria, is a common reason for seeking primary healthcare in rural South and Southeast Asia. However, malaria transmission has declined while health workers are often poorly equipped to manage non-malarial AFIs. This results in indiscriminate antibiotic prescribing and care escalation, which promotes antibiotic resistance and may increase healthcare costs. To address this problem, an electronic clinical decision support algorithm (eCDSA) called 'Electronic clinical Decision support for Acute fever Management (EDAM)' has been developed for primary health workers which integrates clinical, epidemiological and vital sign data with simple point-of-care tests to produce a diagnosis and management plan. METHODS AND ANALYSIS: This is a pragmatic cluster-randomised trial aiming to assess the effect of EDAM and related training on antibiotic prescribing rates in rural Cambodian primary health centres (PHCs) as the primary outcome, along with a range of secondary outcomes including safety. Patients with AFI are eligible for recruitment if they are aged ≥1 year. A cluster is defined as a PHC and PHCs will be randomised to control (standard of care) and intervention (EDAM and associated training) arms, with 15 PHCs per arm. Patients will be followed up after 7 days to ascertain the safety profile of EDAM. Each PHC will recruit 152 patients (total 4560), based on a baseline antibiotic prescription rate of 25% and expected reduction to 17.5% with EDAM. ETHICS AND DISSEMINATION: Results will be published in international peer-reviewed journals to inform the design of future versions of EDAM and of future trials of similar eCDSAs and other digital health interventions targeted towards rural populations. This study was approved by the Oxford University Tropical Research Ethics Committee (550-23) and the Cambodian National Ethics Committee for Health Research (395-NECHR). TRIAL REGISTRATION NUMBER: International Standard Randomized Controlled Trial Number Registry (ISRCTN15157105).

Defining the hidden burden of disease in rural communities in Bangladesh, Cambodia and Thailand: a cross-sectional household health survey protocol.

INTRODUCTION: In low-income and middle-income countries in Southeast Asia, the burden of diseases among rural population remains poorly understood, posing a challenge for effective healthcare prioritisation and resource allocation. Addressing this knowledge gap, the South and Southeast Asia Community-based Trials Network (SEACTN) will undertake a survey that aims to determine the prevalence of a wide range of non-communicable and communicable diseases, as one of the key initiatives of its first project-the Rural Febrile Illness project (RFI). This survey, alongside other RFI studies that explore fever aetiology, leading causes of mortality, and establishing village and health facility maps and profiles, will provide an updated epidemiological background of the rural areas where the network is operational. METHODS AND ANALYSIS: During 2022-2023, a cross-sectional household survey will be conducted across three SEACTN sites in Bangladesh, Cambodia and Thailand. Using a two-stage cluster-sampling approach, we will employ a probability-proportional-to-size sample method for village, and a simple random sample for household, selection, enrolling all members from the selected households. Approximately 1500 participants will be enrolled per country. Participants will undergo questionnaire interview, physical examination and haemoglobin point-of-care testing. Blood samples will be collected and sent to central laboratories to test for chronic and acute infections, and biomarkers associated with cardiovascular disease, and diabetes. Prevalences will be presented as an overall estimate by country, and stratified and compared across sites and participants' sociodemographic characteristics. Associations between disease status, risk factors and other characteristics will be explored. ETHICS AND DISSEMINATION: This study protocol has been approved by the Oxford Tropical Research Ethics Committee, National Research Ethics Committee of Bangladesh Medical Research Council, the Cambodian National Ethics Committee for Health Research, the Chiang Rai Provincial Public Health Research Ethical Committee. The results will be disseminated via the local health authorities and partners, peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT05389540.

Risks and challenges in COVID-19 infection prevention and control in a hospital setting: Perspectives of healthcare workers in Thailand.

INTRODUCTION: In hospital settings, awareness of, and responsiveness to, COVID-19 are crucial to reducing the risk of transmission among healthcare workers and protecting them from infection. Healthcare professionals can offer insights into the practicalities of infection prevention and control (IPC) measures and on how the guideline aimed to ensure adherence to IPC, including use of personal protective equipment (PPE), could best be delivered during the pandemic. To inform future development of such guideline, this study examined the perspectives of healthcare professionals working in a large hospital during the pandemic regarding their infection risks, the barriers or facilitators to implementing their tasks and the IPC measures to protect their safety and health and of their patients. METHOD: In-depth interviews were conducted with 23 hospital staff coming into contact with possible or confirmed cases of COVID-19, or were at potential risk of contracting the disease, including medical doctors, nurses, virology laboratory staff, and non-medical workers. This qualitative study was carried out as part of a knowledge, attitudes and practice survey to prevent COVID-19 transmission at Ramathibodi Hospital in Thailand. We used content analysis to categorize and code transcribed interview data. Existing IPC guideline and evidence synthesis of organisational, environmental, and individual factors to IPC adherence among healthcare workers were used to guide the development of the interview questions and analysis. FINDING: Factors identified as influencing the use of, and adherence to, prevention measures among healthcare workers included knowledge, perceived risk and concerns about the infection. The extent to which these factors were influential varied based on the medical procedures, among other features, that individuals were assigned to perform in the hospital setting. Beyond availability of PPE and physical safety, ease of and readiness to utilize the equipment and implement IPC measures were crucial to motivate hospital staff to follow the practice guideline. Having a ventilated outdoor space for screening and testing, and interaction through mobile technology, facilitated the performance of healthcare workers while reducing the transmission risk for staff and patients. Adequate training, demonstration of guided practices, and streamlined communications are crucial organisational and management support factors to encourage appropriate use of, and adherence to, implementation of infection prevention and control measures among healthcare workers. CONCLUSION: This finding could help inform the development of recommendations to optimise compliance with appropriate use of these measures, and to improve guidance to reduce HCW's risk of disease in hospital settings. Further study should explore the perceptions and experiences of health professionals in smaller health facilities and community-based workers during the pandemic, particularly in resource-limited settings.

Dengue in Myanmar: Spatiotemporal epidemiology, association with climate and short-term prediction.

Dengue is a major public health problem in Myanmar. The country aims to reduce morbidity by 50% and mortality by 90% by 2025 based on 2015 data. To support efforts to reach these goals it is important to have a detailed picture of the epidemiology of dengue, its relationship to meteorological factors and ideally to predict ahead of time numbers of cases to plan resource allocations and control efforts. Health facility-level data on numbers of dengue cases from 2012 to 2017 were obtained from the Vector Borne Disease Control Unit, Department of Public Health, Myanmar. A detailed analysis of routine dengue and dengue hemorrhagic fever (DHF) incidence was conducted to examine the spatial and temporal epidemiology. Incidence was compared to climate data over the same period. Dengue was found to be widespread across the country with an increase in spatial extent over time. The temporal pattern of dengue cases and fatalities was episodic with annual outbreaks and no clear longitudinal trend. There were 127,912 reported cases and 632 deaths from 2012 and 2017 with peaks in 2013, 2015 and 2017. The case fatality rate was around 0.5% throughout. The peak season of dengue cases was from May to August in the wet season but in 2014 peak dengue season continued until November. The strength of correlation of dengue incidence with different climate factors (total rainfall, maximum, mean and minimum temperature and absolute humidity) varied between different States and Regions. Monthly incidence was forecasted 1 month ahead using the Auto Regressive Integrated Moving Average (ARIMA) method at country and subnational levels. With further development and validation, this may be a simple way to quickly generate short-term predictions at subnational scales with sufficient certainty to use for intervention planning.

Epidemiological characteristics and risk factors for cystic and alveolar echinococcosis in China: an analysis of a national population-based field survey.

BACKGROUND: Human cystic and alveolar echinococcosis are neglected tropical diseases that WHO has prioritized for control in recent years. Both diseases impose substantial burdens on public health and the socio-economy in China. In this study, which is based on the national echinococcosis survey from 2012 to 2016, we aim to describe the spatial prevalence and demographic characteristics of cystic and alveolar echinococcosis infections in humans and assess the impact of environmental, biological and social factors on both types of the disease. METHODS: We computed the sex-, age group-, occupation- and education level-specific prevalences of cystic and alveolar echinococcosis at national and sub-national levels. We mapped the geographical distribution of echinococcosis prevalence at the province, city and county levels. Finally, by analyzing the county-level echinococcosis cases combined with a range of associated environmental, biological and social factors, we identified and quantified the potential risk factors for echinococcosis using a generalized linear model. RESULTS: A total of 1,150,723 residents were selected and included in the national echinococcosis survey between 2012 and 2016, of whom 4161 and 1055 tested positive for cystic and alveolar echinococcosis, respectively. Female gender, older age, occupation at herdsman, occupation as religious worker and illiteracy were identified as risk factors for both types of echinococcosis. The prevalence of echinococcosis was found to vary geographically, with areas of high endemicity observed in the Tibetan Plateau region. Cystic echinococcosis prevalence was positively correlated with cattle density, cattle prevalence, dog density, dog prevalence, number of livestock slaughtered, elevation and grass area, and negatively associated with temperature and gross domestic product (GDP). Alveolar echinococcosis prevalence was positively correlated with precipitation, level of awareness, elevation, rodent density and rodent prevalence, and negatively correlated with forest area, temperature and GDP. Our results also implied that drinking water sources are significantly associated with both diseases. CONCLUSIONS: The results of this study provide a comprehensive understanding of geographical patterns, demographic characteristics and risk factors of cystic and alveolar echinococcosis in China. This important information will contribute towards developing targeted prevention measures and controlling diseases from the public health perspective.

Temporal trends in severe malaria in Chittagong, Bangladesh.

BACKGROUND: Epidemiological data on malaria in Bangladesh are sparse, particularly on severe and fatal malaria. This hampers the allocation of healthcare provision in this resource-poor setting. Over 85% of the estimated 150,000-250,000 annual malaria cases in Bangladesh occur in Chittagong Division with 80% in the Chittagong Hill Tracts (CHT). Chittagong Medical College Hospital (CMCH) is the major tertiary referral hospital for severe malaria in Chittagong Division. METHODS: Malaria screening data from 22,785 inpatients in CMCH from 1999-2011 were analysed to investigate the patterns of referral, temporal trends and geographical distribution of severe malaria in Chittagong Division, Bangladesh. RESULTS: From 1999 till 2011, 2,394 malaria cases were admitted, of which 96% harboured Plasmodium falciparum and 4% Plasmodium vivax. Infection was commonest in males (67%) between 15 and 34 years of age. Seasonality of malaria incidence was marked with a single peak in P. falciparum transmission from June to August coinciding with peak rainfall, whereas P. vivax showed an additional peak in February-March possibly representing relapse infections. Since 2007 there has been a substantial decrease in the absolute number of admitted malaria cases. Case fatality in severe malaria was 18% from 2008-2011, remaining steady during this period.A travel history obtained in 226 malaria patients revealed only 33% had been to the CHT in the preceding three weeks. Of all admitted malaria patients, only 9% lived in the CHT, and none in the more remote malaria endemic regions near the Indian border. CONCLUSIONS: The overall decline in admitted malaria cases to CMCH suggests recent control measures are successful. However, there are no reliable data on the incidence of severe malaria in the CHT, the most endemic area of Bangladesh, and most of these patients do not reach tertiary health facilities. Improvement of early treatment and simple supportive care for severe malaria in remote areas and implementation of a referral system for cases requiring additional supportive care could be important contributors to further reducing malaria-attributable disease and death in Bangladesh.

Diagnostic accuracy of the WHO clinical definitions for dengue and implications for surveillance: A systematic review and meta-analysis.

BACKGROUND: Dengue is the world's most common mosquito-borne virus but remains diagnostically challenging due to its nonspecific presentation. Access to laboratory confirmation is limited and thus most reported figures are based on clinical diagnosis alone, the accuracy of which is uncertain. This systematic review assesses the diagnostic accuracy of the traditional (1997) and revised (2009) WHO clinical case definitions for dengue fever, the basis for most national guidelines. METHODOLOGY/PRINCIPAL FINDINGS: PubMed, EMBASE, Scopus, OpenGrey, and the annual Dengue Bulletin were searched for studies assessing the diagnostic accuracy of the unmodified clinical criteria. Two reviewers (NR/SL) independently assessed eligibility, extracted data, and evaluated risk of bias using a modified QUADAS-2. Additional records were found by citation network analysis. A meta-analysis was done using a bivariate mixed-effects regression model. Studies that modified criteria were analysed separately. This systematic review protocol was registered on PROSPERO (CRD42020165998). We identified 11 and 12 datasets assessing the 1997 and 2009 definition, respectively, and 6 using modified criteria. Sensitivity was 93% (95% CI: 77-98) and 93% (95% CI: 86-96) for the 1997 and 2009 definitions, respectively. Specificity was 29% (95% CI: 8-65) and 31% (95% CI: 18-48) for the 1997 and 2009 definitions, respectively. Diagnostic performance suffered at the extremes of age. No modification significantly improved accuracy. CONCLUSIONS/SIGNIFICANCE: Diagnostic accuracy of clinical criteria is poor, with significant implications for surveillance and public health responses for dengue control. As the basis for most reported figures, this has relevance to policymakers planning resource allocation and researchers modelling transmission, particularly during COVID-19.

Study protocol: an open-label individually randomised controlled trial to assess the efficacy of artemether-lumefantrine prophylaxis for malaria among forest goers in Cambodia.

INTRODUCTION: In the Greater Mekong Subregion, adults are at highest risk for malaria. The most relevant disease vectors bite during daytime and outdoors which makes forest work a high-risk activity for malaria. The absence of effective vector control strategies and limited periods of exposure during forest visits suggest that chemoprophylaxis could be an appropriate strategy to protect forest goers against malaria. METHODS AND ANALYSIS: The protocol describes an open-label randomised controlled trial of artemether-lumefantrine (AL) versus multivitamin as prophylaxis against malaria among forest goers aged 16-65 years in rural northeast Cambodia. The primary objective is to compare the efficacy of the artemisinin combination therapy AL versus a multivitamin preparation as defined by the 28-day PCR parasite positivity rate and incidence of confirmed clinical malaria of any species. The sample size is 2200 patient-episodes of duration 1 month in each arm. The duration of follow-up and prophylaxis for each participant is 1, 2 or 3 consecutive 28-day periods, followed by a further 28 days of post-exposure prophylaxis, depending on whether they continue to visit the forest. Analysis will be done both by intention to treat and per protocol. ETHICS AND DISSEMINATION: All participants will provide written, informed consent. Ethical approval was obtained from the Oxford Tropical Research Ethics Committee and the Cambodia National Ethics Committee for Health Research. Results will be disseminated by peer-reviewed open access publication together with open data. TRIAL REGISTRATION NUMBER: NCT04041973; Pre-result.

An interactive application for malaria elimination transmission and costing in the Asia-Pacific.

Leaders in the Asia-Pacific have endorsed an ambitious target to eliminate malaria in the region by 2030. The emergence and spread of artemisinin drug resistance in the Greater Mekong Subregion makes elimination urgent and strategic for the global goal of malaria eradication. Mathematical modelling is a useful tool for assessing and comparing different elimination strategies and scenarios to inform policymakers. Mathematical models are especially relevant in this context because of the wide heterogeneity of regional, country and local settings, which means that different strategies are needed to eliminate malaria. However, models and their predictions can be seen as highly technical, limiting their use for decision making. Simplified applications of models are needed to allow policy makers to benefit from these valuable tools. This paper describes a method for communicating complex model results with a user-friendly and intuitive framework. Using open-source technologies, we designed and developed an interactive application to disseminate the modelling results for malaria elimination. The design was iteratively improved while the application was being piloted and extensively tested by a diverse range of researchers and decision makers. This application allows several target audiences to explore, navigate and visualise complex datasets and models generated in the context of malaria elimination. It allows widespread access, use of and interpretation of models, generated at great effort and expense as well as enabling them to remain relevant for a longer period of time. It has long been acknowledged that scientific results need to be repackaged for larger audiences. We demonstrate that modellers can include applications as part of the dissemination strategy of their findings. We highlight that there is a need for additional research in order to provide guidelines and direction for designing and developing effective applications for disseminating models.

Malaria elimination transmission and costing in the Asia-Pacific: Developing an investment case.

Background: The Asia-Pacific region has made significant progress against malaria, reducing cases and deaths by over 50% between 2010 and 2015. These gains have been facilitated in part, by strong political and financial commitment of governments and donors. However, funding gaps and persistent health system challenges threaten further progress. Achieving the regional goal of malaria elimination by 2030 will require an intensification of efforts and a plan for sustainable financing. This article presents an investment case for malaria elimination to facilitate these efforts. Methods: A transmission model was developed to project rates of decline of Plasmodium falciparum and Plasmodium vivax malaria and the output was used to determine the cost of the interventions that would be needed for elimination by 2030. In total, 80 scenarios were modelled under various assumptions of resistance and intervention coverage. The mortality and morbidity averted were estimated and health benefits were monetized by calculating the averted cost to the health system, individual households, and society. The full-income approach was used to estimate the economic impact of lost productivity due to premature death and illness, and a return on investment was computed. Results: The study estimated that malaria elimination in the region by 2030 could be achieved at a cost of USD 29.02 billion (range: USD 23.65-36.23 billion) between 2017 and 2030. Elimination would save over 400,000 lives and avert 123 million malaria cases, translating to almost USD 90 billion in economic benefits. Discontinuing vector control interventions and reducing treatment coverage rates to 50% will result in an additional 845 million cases, 3.5 million deaths, and excess costs of USD 7 billion. Malaria elimination provides a 6:1 return on investment. Conclusion: This investment case provides compelling evidence for the benefits of continued prioritization of funding for malaria and can be used to develop an advocacy strategy.